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Design and development of polymethylmethacrylate-grafted gellan gum (PMMA-g-GG)-based pH-sensitive novel drug delivery system for antidiabetic therapy

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Abstract

The objective of the present study was to develop a pH-sensitive drug delivery system by using polymethylmethacrylate-grafted gellan gum (PMMA-g-GG). PMMA-g-GG was synthesized by free radical polymerization reaction by using redox initiator ceric ammonium nitrate (CAN), and a series of graft copolymers were prepared with varying concentrations of methylmethacrylate (MMA) and CAN. Grafting parameters such as the percentage and efficiency of grafting were calculated, and the effect of monomer as well as initiator concentration was studied on the grafting yield. Optimization was done by one optimal response surface methodology. The batch with a better percentage grafting and grafting efficiency was selected and characterized by elemental analysis (CHN), FT-IR, DSC, PXRD, 1H-NMR, and SEM. Furthermore, acute oral toxicity study and histopathological analysis suggested non-toxic and biocompatible nature of the grafted gum. Metformin hydrochloride pellets were prepared using PMMA-g-GG, characterized in detail, and assessed for biocompatibility and efficacy. PMMA-g-GG-based formulation (M4) exhibited a pH-sensitive as well as sustained release of the drug over the period of 12 h and the release profile followed Peppas model. In vivo efficacy studies indicated a promising antidiabetic potential of the prepared formulation. Thus, PMMA-g-GG-based formulations can be implicated as novel drug delivery systems for facilitated antidiabetic therapy in the near future.

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Acknowledgments

The author(s) express their gratitude for the financial support provided by the Department of Science and Technology, Government of India, New Delhi, India, under grant SR/SO/HS-0107/2016. Author(s) express deep sense of gratitude towards Central Food Technological Research Institute (CFTRI), Mysuru (a constituent laboratory of CSIR, New Delhi) and JSS Academy of Higher Education and Research (JSSAHER), Mysuru, for provision of obligatory facilities to carry out present research work. The author(s) are profusely thankful to Dr. Ekta Singh, Department of Biosciences and Bioengineering (BSBE), Indian Institute of Technology Bombay (IITB), Mumbai, for proof reading and constructive suggestions.

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  1. Rohit R. Bhosale and Riyaz Ali M. Osmani contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutics, Krishna Institute of Pharmacy, Krishna Institute of Medical Sciences Deemed To Be University, Karad, Maharashtra, 415539, India

    Rohit R. Bhosale

  2. Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka, 570015, India

    Hosahalli V. Gangadharappa & Devegowda V. Gowda

  3. Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, 400076, India

    Riyaz Ali M. Osmani

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  1. Rohit R. Bhosale
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Correspondence to Riyaz Ali M. Osmani.

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Bhosale, R.R., Gangadharappa, H.V., Osmani, R.A.M. et al. Design and development of polymethylmethacrylate-grafted gellan gum (PMMA-g-GG)-based pH-sensitive novel drug delivery system for antidiabetic therapy. Drug Deliv. and Transl. Res. 10, 1002–1018 (2020). https://doi.org/10.1007/s13346-020-00776-7

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